PROJECT SUMMARY/ABSTRACT Blood flow and blood oxygenation are both important physiological markers of tissue health and function that can be quantitatively measured using two independent but complementary diffuse optical technologies. Diffuse Correlation Spectroscopy (DCS) measures the fluctuations in intensity of coherently scattered light to estimate blood flow, and multi-distance Diffuse Optical Spectroscopy (DOS) estimates blood oxygenation from the absorption of light by tissue. While the two optical techniques can be combined into a single hybrid fiber optic probe, differences in the respective volume of tissue interrogated by DCS/DOS could result in systemic errors in estimation of optical properties ? especially when using multi-distance measurements in heterogeneous tissues. As a result, the accuracy and reliability of hemodynamic responses due to focal changes in tissue function, such as due to functional activation or due to localized tumors, are poor. This research proposal addresses these issues, and develops a new diffuse optical technique, Frequency Domain Diffuse Correlation Spectroscopy (FD- DCS), to simultaneously measure blood flow and blood oxygenation from a single set of measurements without confounding partial volume effects. More specifically, we develop a generalized tissue light propagation model that fully describes the diffusion of temporal light fluctuations through tissue, and related instrumentation to leverage this approach, to estimate static (tissue absorption and reduced scattering coefficients) and dynamic (tissue blood flow) properties. We characterize coherence, modulation and noise characteristics of the FD-DCS technique using experiments in tissue simulating phantoms. In addition, we validate the new technique against existing technologies (and theoretical expectations) via controlled measurements of absorption/scattering coefficients, and flow in tissue simulating phantoms. Finally, we perform preliminary in vivo feasibility experiments, to demonstrate and validate the instrument in a biological setting.